Serotonergic modulation of pain and analgesic responses: a study in rats with constitutionally altered serotonin transporters.

BACKGROUND: A role of the serotonin (5HT) transporter, a key regulator of serotonergic transmission, in the physiology, pharmacology and genetics of pain responses has been proposed recently. The present study aimed to explore the impact of constitutive differences in the activity of the serotonin transporter, and 5HT homeostasis in general, on the modulation on pain sensitivity and analgesic responses to drugs that utilize 5HT mechanisms. METHODS: A novel genetic animal model, Wistar-Zagreb 5HT rats, obtained by selective breeding of animals for extreme activity of the platelet serotonin transporter was used. As a consequence of breeding, two sublines of this model, termed high-5HT and low-5HT, differ in both central and peripheral serotonin homeostasis. Thermal pain sensitivity of 5HT sublines was assessed at baseline and following administration of analgesic drugs, as determined by paw withdrawal latency to radiant heat stimulation. RESULTS: Animals from 5HT sublines show differences in both basal pain sensitivity and analgesic responses. Rats with the low-5HT phenotype displayed decreased baseline paw withdrawal latencies (hyperalgesia) in comparison to their high-5HT counterpart (25%; p < 0.001). They also showed better analgesic response to acute and prolonged treatment with tramadol (p = 0.027) and clomipramine (p = 0.019), respectively, whereas administration of fluvoxamine did not produce an analgesic effect in either 5HT subline. CONCLUSIONS: These findings support the idea that functionality of the serotonin transporter is one of the physiological/genetic determinants of individual differences in pain responses and modulation. They also validate Wistar-Zagreb 5HT rats, with constitutionally up-regulated/down-regulated serotonin transporter, as a potential new genetic model for studying serotonergic modulation of pain responses.

Infrared digital thermography of scrotum in early selection of progressive varicocele.

Varicocele is frequent but correctable cause of male infertility. Varicocelectomy is the most commonly performed operative procedure for varicocele. Majority of varicocele patients do not have fertility problem, therefore surgical correction is not recommended in all prevalent cases. On the other hand, varicocele is a progressive condition in some cases and individual with varicocele is at risk for developing impairment which can ultimately lead to semen deterioration and consequent infertility. Selection of patients with varicocele that will progress and cause infertility is beyond our current diagnostic capabilities. Diagnostic assessment of varicocele depends on physical examination and scrotal ultrasound/doppler. Infrared digital thermography of scrotum is a non-invasive and objective diagnostic method for early varicocele detection by means of temperature measurement on the scrotal skin surface. The criteria for diagnostic use of scrotal thermography were recently presented. We hypothesize that the infrared digital thermography of scrotum could be the cornerstone in detection of varicoceles that tend to progress with impairment of semen quality and will require surgical correction, among all prevalent varicocele cases.

Scrotal infrared digital thermography in assessment of varicocele--pilot study to assess diagnostic criteria.

The aim of this study was to assess scrotal thermography in diagnostics of varicocele and suggest potential diagnostic criteria. Twelve patients with clinically diagnosed varicocele were examined with scrotal infrared digital thermography, physical examination and ultrasound/doppler. The main outcome measure was evaluation of thermography diagnostic criteria for varicocele. Mean temperature at left pampiniform plexus was ≥ 34 °C in 83%, and at right pampiniform plexus in all cases was ≤ 34 °C. In 92% of patients, temperature at the left testicle was ≥ 32 °C, whereas at the right testicle it was >32 °C in 50% patients. Temperatures between left and right pampiniform plexus and between left and right testicle were significantly different with P < 0.0001 and P < 0.006 respectively. In all patients, temperature difference between pampiniform plexuses was ≥ 0.6 °C. In 92% of patients, temperature at left pampiniform plexus was equal or higher to thigh temperature with the mean temperature difference of 1.1 ± 1.1 °C. Temperature at right pampiniform plexus was colder than the thigh in 92% of patients. This study suggests diagnostic criteria of five thermographic signs to easily diagnose varicocele. Scrotal thermography presents feasible, short and low cost diagnostic method for varicocele. Further study on a larger number of patients and healthy participants is needed to evaluate sensitivity and specificity of this method.

Therapeutic agents utilized in urban/rural prehospital care.

INTRODUCTION: Objectives of this study were to determine the number of prehospital emergency patients who were given advanced life support (ALS) drugs and to compare utilization rates for ALS drugs in urban and rural environments. Certified ALS emergency medical technicians (Arizona) have 29 therapeutic agents authorized for prehospital administration. These agents may be administered only under direction of a medical control authority or by following standing orders. METHODS: A retrospective review was made of prehospital emergency encounter records. They were acquired by the Arizona Office of Emergency Medical Services (OEMS) from rural EMS providers who used optically scannable forms and from a metropolitan fire department's medical emergency response records. RESULTS: In 1989 and 1990, 273,611 emergency patient encounter records were entered into the EMS database; 197,260 were urban responses and 76,351 were rural responses. Drugs (ALS) were administered to 16,730 (8.5%) urban emergency patients and to 5,359 (7%) rural emergency patients at the incident site or during transport to a medical care facility. Nitrostat, 0.4 mg sublingual tablet, was the drug most frequently administered to emergency patients in the prehospital setting. Utilization rates found in the urban and the rural data sets were consistent for the individual agents. Variations in use frequency between urban and rural setting were noted for some drugs. Of the 29 approved ALS drugs, seven (24%) were administered to 10% or more urban patients who received drugs. In the rural areas, eight (27.6%) were administered to 10% or more patients who received drugs. There were nine (31%) agents administered to less than 1% of all patients who received drugs. A majority of the approved drugs, 17 (59%) were administered at a rate below 5% of all patients receiving medications. CONCLUSION: Severity of illness or injury prompted administration of ALS drugs to 8.1% of patients receiving prehospital emergency care. The most frequently utilized medication in the urban/rural areas was for treatment of cardiac symptoms. Variations between urban/rural drug utilization reflected the drugs of choice which are compatible with long transport times to a medical facility.